TY - JOUR T1 - SULT4A1 Protects Against Oxidative-Stress Induced Mitochondrial Dysfunction JF - Drug Metabolism and Disposition JO - Drug Metab Dispos DO - 10.1124/dmd.119.088047 SP - dmd.119.088047 AU - Shaida A Andrabi AU - Mohammed I Hossain AU - Joshua M Marcus AU - Jun Hee Lee AU - Patrick L Garcia AU - Jean-Philippe Gagne AU - Guy G Poirier AU - Charles N Falany Y1 - 2019/01/01 UR - http://dmd.aspetjournals.org/content/early/2019/07/02/dmd.119.088047.abstract N2 - Sulfotransferase 4A1 (SULT4A1), a member of cytosolic sulfotransferases (SULT) is exclusively expressed in neurons with no known function. Severe phenotype and early postnatal death in SULT4A1 knock out mice revealed that SULT4A1 is an essential neuronal protein. Localization of SULT4A1 in different cytosolic compartments, including mitochondria, suggests multiple roles for this protein. We observed that knockdown of SULT4A1 results in the accumulation of reactive oxygen species in primary cortical neurons, suggesting a potential role of SULT4A1 in regulating redox homeostasis. Expression of SULT4A1 in the human neuroblastoma SH-SY5Y cells revealed a defused but non-uniform staining pattern in the cytoplasm, with increased density around mitochondria. Subcellular fractionation of SULT4A1 expressing SH-SY5Y cells confirms the presence of SULT4A1 in mitochondrial fractions. SULT4A1 expressing cells display significant protection against H2O2-mediated defects in mitochondrial function and loss of mitochondrial membrane potential. Expression of SULT4A1 in SH-SY5Y cells also protects against H2O2-induced cell death. These data indicate that SULT4A1 protects mitochondria against oxidative damage, and may be an essential pharmacological target in neural diseases involving mitochondrial dysfunction and oxidative stress.SIGNIFICANCE STATEMENT Studies on SULT4A1 knock out mice suggest that SULT4A1 plays a vital role in neuronal function and survival via yet undefined mechanisms. Our data demonstrate that depletion of SULT4A1 induces oxidative stress in neurons and expression of SULT4A1 in SH-SY5Y cells protects against oxidative-stress-induced mitochondrial dysfunction and cell death. These results suggest that SULT4A1 may have a crucial protective function against mitochondrial dysfunction and oxidative stress, and may serve a potential therapeutic target in different neurological diseases involving mitochondrial dysfunction and oxidative stress. ER -